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Product Name: Clonazepam

Generics: Clonazepam

Common Brand Names: Klonopin; Rivotril

Pharmaceutical Category: Antidepressants / Anti Anxiety

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There is an additional general information about this medication active ingredient clonazepam:

Pharmacological action

Clonazepam is an antiepileptic drugs from the group of benzodiazepine derivatives. This medication has a pronounced anticonvulsant and central muscle relaxant, anxiolytic, sedative and hypnotic effects.
Clonazepam strengthens the inhibitory effect of GABA on the transmission of nerve impulses.
Anxiolytic effects of this drug is due to the influence on the amygdaloid complex of the limbic system and appears in reducing the emotional stress, reduce anxiety, fear, anxiety.
The sedation effects is due to the influence on the reticular formation of the brainstem and nonspecific thalamic nucleus and manifests a decrease in neurotic symptoms (anxiety, fear).
Anticonvulsant effect is realized by increasing presynaptic inhibition.
The central muscle relaxant effect is due to inhibition of spinal polysynaptic afferent inhibitory ways (to a lesser extent and monosynaptic).
It is possibly and direct inhibition of motor nerves and muscle function.

Pharmacokinetics

For oral administration of Clonazepam its bioavailability is more than 90%. The plasma protein binding is more than 80%. Vd is 3.2 L / kg. T1/2 is 23 hours. This drug is excreted mainly as metabolites.

Why is Clonazepam prescribed?

As the medication of I row - epilepsy (adults, infants and young children): typical absence seizures (petit mal), atypical absence seizures (Lennox-Gastaut syndrome), nodding spasm, atonic seizures (a syndrome of "falling" or "drop-attacks").
As the medication of II row - infantile spasms (West syndrome).
As the medication of III row - tonic-clonic seizures (grand mal), simple and complex partial seizures and secondary generalized tonic-clonic seizures.
Status epilepticus (IV injections).
Somnambulism, muscular hypertonicity, insomnia (especially in patients with organic brain damage), psychomotor agitation, alcohol withdrawal syndrome (acute agitation, tremor, threatening or acute delirium tremens and hallucinations), panic disorder.

Dosage and administration

Dosing regimen of Clonazepam is individual. For oral administration for adults the recommended initial dose is not more than 1 mg / day. The maintenance dose is 4-8 mg / day.
For infants and children aged 1-5 years, the initial dose should not exceed 250 micrograms / day, for children aged 5-12 years - 500 mcg / day. Supporting daily doses for children under 1 year are 0.5-1 mg, 1-5 years - 1-3 mg, 5-12 years - 3-6 mg.
For elderly patients the recommended starting dose is not exceeding 500 micrograms.
The daily dose should be divided into 3-4 equal doses. Maintenance doses prescribed in 2-3 weeks of treatment.
IV (slowly) for adults - 1 mg, for children under the age of 12 years - 500 mcg.

Clonazepam side effects, adverse reactions

CNS: early treatment - severe lethargy, fatigue, drowsiness, weakness, dizziness, stupor, headache; rarely - confusion, ataxia. When used in high doses, especially in long-term treatment - violation of articulation, diplopia, nystagmus, paradoxical reactions (including acute excitation states); anterograde amnesia. Rarely - hyperergic reactions, muscle weakness - depression. With long-term treatment of some forms of epilepsy may increase the frequency of seizures.
Digestive system: rarely - dry mouth, nausea, diarrhea, heartburn, nausea, vomiting, decreased appetite, constipation or diarrhea, liver damage, elevated liver transaminases and alkaline phosphatase, jaundice. In infants and young children may increase salivation.
Cardiovascular system: decreased blood pressure, tachycardia.
Endocrine: changes in libido, dysmenorrhea, reversible premature sexual development in children (part-time early puberty).
Respiratory system: with / in the introduction possible respiratory depression, particularly after treatment with other medicines that cause respiratory depression; in infants and young children it is possible bronchial hypersecretion.
Hematopoietic system: leukopenia, neutropenia, agranulocytosis, anemia, and thrombocytopenia.
Urinary system: urinary incontinence, urinary retention, impaired renal function.
Allergic reactions: hives, skin rash, itching, extremely rare - anaphylactic shock.
Dermatological reactions: transient alopecia, discoloration.
Other: addiction, drug dependence, with a sharp decrease in dose or cessation of reception - a withdrawal syndrome.

Clonazepam contraindications

Inhibition of the respiratory center, severe COPD (the progression of the degree of respiratory failure), acute respiratory failure, myasthenia gravis, coma, shock, angle-closure glaucoma (acute attack or predisposition), acute alcohol intoxication with the weakening of the vital functions, acute poisoning with narcotic analgesics and hypnotics, severe depression (suicidal tendencies may occur), pregnancy, lactation, hypersensitivity to clonazepam.

Using during pregnancy and breastfeeding

Clonazepam is contraindicated for use during pregnancy and lactation. This medication crosses the placental barrier. Clonazepam may be excreted in breast milk.
Category effects on the fetus by FDA - D.

Special instructions

With caution used in patients with ataxia, severe liver disease, severe chronic respiratory failure, especially in the acute stage of deterioration, with episodes of sleep apnea.
With careful use in elderly patients because they may be slowed by removal of clonazepam and reduced tolerance, especially in the presence of cardio-pulmonary insufficiency.
With prolonged use of this drug it may develop drug dependence. With a sharp lifting of clonazepam after long-term treatment it may been developed the withdrawal syndrome.
In long-term use of Clonazepam in children should be kept in mind the possibility of side effects on physical and mental development, which may not manifest for years.
During the period of treatment avoid to drink alcohol.
During the period of treatment is observed slowing of psychomotor responses. It is necessary to take into account persons engaged in potentially hazardous activities that require attention and quickness of psychomotor reactions.

Clonazepam drug interactions

Simultaneous administration of Clonazepam with:
  • drugs providing a depressing effect on the CNS, ethanol, ethanol containing drugs may increase the CNS depressant effects.
  • Clonazepam enhances the action of muscle relaxants, with valproate sodium reducing sodium valproate and the provocation of seizures.
  • described the case to reduce the concentration of desipramine in plasma in 2 times and its increase after withdrawal of clonazepam.
  • carbamazepine which causes the induction of microsomal liver enzymes may increase metabolism and the resulting decrease in concentration of clonazepam in plasma.
  • caffeine may reduce sedative and anxiolytic effects of clonazepam, with lamotrigine - may decrease the concentration of clonazepam in plasma, with lithium carbonate - the development of neurotoxicity.
  • primidone increases its concentration in blood plasma, with tiapride - possibly the development of NMS.
  • toremifene it is possible significant reduction in AUC and T1/2 of toremifene in connection with the induction of liver enzymes under the influence of clonazepam which leads to faster metabolism of toremifene.
  • may increase the concentration of phenytoin in blood plasma and the development of toxic reactions, its reduction or absence of these changes.
  • cimetidine increases the side effects of the CNS, however, the frequency of seizures in some patients decreased. There was described a case of headache with localization in the occipital region, while the application with phenelzine.


    Clonazepam in case of emergency / overdose

    Symptoms: CNS depression of varying severity (from lethargy to coma): severe drowsiness, prolonged confusion, depression of reflexes, coma, possible respiratory depression.
    Treatment: induction of vomiting and the prescription of activated charcoal (if the patient is conscious), gastric lavage through a tube (if patient is unconscious), symptomatic therapy, monitoring of vital functions (breathing, pulse, blood pressure), in intravenous fluids (to increase urine output), if necessary, mechanical ventilation. As a specific antidote may be used benzodiazepine receptor antagonist flumazenil (in hospital), however, flumazenil is not indicated for use in patients with epilepsy (likely provocation of epileptic seizures).

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